Ion-selective electrode (ISE) techniques are routinely used in the clinical chemistry laboratories for the determination of sodium, potassium, or chloride. These ions are important regulators of various physiological functions, thus their monitoring/determination in patient samples (e.g. serum, plasma, or urine) is of great importance.
The underlying measurement principle is potentiometry. Devices employing ISEs use a measurement electrode, which is ideally selective only for the ion it should measure, and a reference electrode, which delivers a stable potential against which the measurement electrode's potential is read.
The sample (e.g. human serum, plasma, or urine) is placed in the sample channel in front of the ion selective membrane. A potential develops over this membrane, which under ideal circumstances only depends on the activity of the ion to be measured (the analyte).
That potential is derived via the contact pin and read against a stable signal delivered by the reference electrode. This reference electrode is the other half-cell of the measurement circuit.
The potential difference measured between the measurement electrode and the reference electrode is related to the concentration of the ion in question employing the Nernst equation as described e.g. in chapter of the book K Cammann, H Galster “Das Arbeiten mit ionenselektiven Elektroden”, 3rd edition, Springer Verlag, 1996.
Each sample measurement consists of two separate measurements: the measurement of the sample material itself, and the subsequent one-point calibration. The one-point calibration is the measurement of a one-point calibrator of known concentration. The results of both, sample and one-point calibration measurement are expressed in millivolt.
These results, together with the electrode slope and other parameters determined during the main calibration (i.e. a two-point calibration), are used for the calculation of the final sample result (i.e. ion concentration), usually expressed in mmol/L (millimole per liter).
In clinical chemistry analyzers from various manufacturers, ISE modules containing sodium, potassium, and chloride selective electrodes are used for the routine determinations of those ions in human body fluid samples (such as serum, plasma, or urine) for diagnostic purposes. These modules allow the simultaneous determination of the analyte concentrations in one measurement from a given sample.
The results generated by such modules are of significant clinical relevance, and therefore care must be taken to ensure result integrity under all circumstances. Thus, the results are subjected to several checks and plausibility controls prior their display on an instrument, or distribution to electronic laboratory information systems.
If, for instance, the signal generated for a given electrode (e.g. sodium) does not fulfill pre-defined criteria for the signal stability over time, a flag is generated and attached to the result informing the physician that the validity of the result may be doubtful. Samples for which flagged measurement results are obtained, are routinely re-analyzed, and for this purpose measurement of the sample in the ISE module is repeated.
Since in clinical chemistry it is very important to obtain accurate measurement results especially of the concentrations of sodium and potassium in biological samples, it is desirable to eliminate even very minute error possibilities.
A possible cause of a measurement error is the alteration of the measurement conditions, e.g. by the appearance of air bubbles in the sample channel.
Another possible cause of a measurement error are electrostatic discharges entering the shielded measuring compartment of an ISE module via waste lines and/or not properly grounded mechanical mounting parts. Such electrostatic discharges can cause shifts in the reference potential.
Such alterations can adversely influence the measurement results, because the potential difference measured between the measurement electrode and the reference electrode e.g. for the one-point calibration is used for the calculation of the concentrations of the analytes (e.g. sodium and potassium) in biological samples.
Deviations of the potential differences measured with ion-selective electrodes caused by relatively large disturbances are detected by known test and plausibility checks implemented in ISE modules. Small deviations of the potential differences measured with ion-selective electrodes as those caused by the above mentioned air-bubbles and electrostatic discharges, however, may remain undetected, and still adversely affect the measurement results.
The detection of small but abnormal deviations of the potential differences measured with ion-selective electrodes is difficult, because some of those deviations are not indicative for any malfunction or problem, but simply correspond to a concentration value which is higher or lower than an expected normal value.
In view of the foregoing, it is desirable to ensure that at one hand all questionable deviations, i.e. deviations of doubtful origin, are identified, and on the other hand, that valid measurement results are not identified as doubtful, since this would lead to unnecessary repetition of (correct) sample measurements, and this causes unnecessary work and expenses and delays in the delivery of the measurement results.